Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and remains incurable despite multimodal intensive treatment regimens. Brain tumors can be difficult to biopsy due to their high-risk location relative to vital structures of the brain or patient related co-morbidity. A very limited number of patients are re-biopsied or re-resected when they relapse after the initial therapy. The management of these patients also poses many problems as follow up of patients with brain tumor is limited to radiological techniques such as magnetic resonance imaging (MRI). Even with the addition of the last generation of imaging studies (spectro-MRI, PET-CT), clinical assessment of tumor progression versus pseudo-progression remains difficult. This can pose serious delays in treatment decision and result in harm to the patient. Management of patients with brain tumor is problematic as it is limited to radiological techniques and clinical assessment of tumor progression versus pseudo-progression remains difficult.
The use of tumor-specific rearrangements to monitor the status of the disease may improve the clinical management of brain tumor patients. EGFRvIII is a truncated extracellular mutant of the epithelial growth factor receptor (EGFR) commonly found in GBMs that confers enhanced tumorigenic behavior. GBM patients testing positive for EGFRvIII have a bleaker prognosis than those who don't. Virtually no EGFRvIII-positive patient survives two years, versus about 15% of those who are EGFRvIII-negative. EGFRvIII is tumor specific and is present in about one third of brain tumor cases. Thus, it potentially represents an ideal mutation to follow and quantify in the peripheral blood of patients on treatment. However, detecting this mutation in the genomic DNA is challenging as the deletion breakpoint is different from one patient to another. Thus, the need exists for new methods and kits that allow for the detection and monitoring of EGFRvIII in patients suffering from GBM.